[Prevalence of sleep-related breathing disorders of inpatients with psychiatric disorders]. / Prävalenz schlafbezogener Atmungsstörungen bei stationären Patienten mit psychischen Erkrankungen.

BACKGROUND: Sleep-related breathing disorders seriously impair well-being and increase the risk for relevant somatic and psychiatric disorders. Moreover, risk factors for sleep-related breathing disorders are highly prevalent in psychiatric patients. The aim of this study was for the first time in Germany to study the prevalence of obstructive sleep apnea syndrome (OSAS) as the most common form of sleep-related breathing disorder in patients with psychiatric disorders. METHODS: In 10 psychiatric hospitals in Germany and 1 hospital in Switzerland, a total of 249 inpatients underwent an 8­channel sleep polygraphy to investigate the prevalence of sleep apnea in this group of patients. RESULTS: With a conspicuous screening result of 23.7% of the subjects, a high prevalence of sleep-related breathing disorders was found to occur among this group of patients. Male gender, higher age and high body mass index (BMI) were identified as positive risk factors for the detection of OSAS. DISCUSSION: The high prevalence indicates that sleep apnea is a common sleep disorder among psychiatric patients. Although OSAS can lead to substantial disorders of the mental state and when untreated is accompanied by serious somatic health problems, screening procedures are not part of the routine work-up in psychiatric hospitals; therefore, sleep apnea is presumably underdiagnosed in psychiatric patients. In view of the results of this and previous studies, this topic complex should be the subject of further research studies.

[Association of Deployment and Tobacco Dependence among Soldiers]. / Zusammenhang von Auslandseinsätzen und Tabakabhängigkeit bei Soldaten.

OBJECTIVE: Smoking is a highly preventable risk factor. The present study investigates whether military operations abroad, as compared to deployment preparation, increase the risk of starting to smoke, enhance tobacco dependence and moderator variables can be identified on smoking behavior. METHOD: The study was conducted at 2 mechanized infantry battalions with N=264 soldiers. The task force completed a deployment in Afghanistan, the control group performed a deployment training. Assessments of tobacco dependence, posttraumatic symptoms, depression and stress were done before (t1) and after (t3) deployment. In addition, one assessment was done at mid-point (t2) during deployment and during the pre-deployment training, respectively. RESULTS: The prevalence rate of smoking soldiers was 56,4%. 51,1% (n=135) of all examined soldiers smoked more than 20 cigarettes per day. The results show a significant increase of tobacco dependence in the task force from t1 to t3 (p=0,040) as compared to the control group. For both groups, there was no increase in starting to smoke during the period of investigation (χ²<1; n. s.). Moderator variables on smoking were not found, but there was a significant increase in posttraumatic stress symptoms in the deployed group (p=0,006). CONCLUSIONS: Perhaps the increase in tobacco dependence in the experimental group can be attributed to the specific burdens of deployment. If high smoking rates were to be found also in other branches of the armed services, effective smoking cessation programs should be offered more widely.

Antidepressants, autonomic function and mortality in patients with coronary heart disease: data from the Heart and Soul Study.

BACKGROUND: Antidepressants reduce depressive symptoms in patients with coronary heart disease, but they may be associated with increased mortality. This study aimed to examine whether the use of tricyclic antidepressants (TCA) or selective serotonin reuptake inhibitors (SSRI) is associated with mortality in patients with coronary heart disease, and to determine whether this association is mediated by autonomic function. METHOD: A total of 956 patients with coronary heart disease were followed for a mean duration of 7.2 years. Autonomic function was assessed as heart rate variability, and plasma and 24-h urinary norepinephrine. RESULTS: Of 956 patients, 44 (4.6%) used TCA, 89 (9.3%) used SSRI, and 823 (86.1%) did not use antidepressants. At baseline, TCA users exhibited lower heart rate variability and higher norepinephrine levels compared with SSRI users and antidepressant non-users. At the end of the observational period, 52.3% of the TCA users had died compared with 38.2% in the SSRI group and 37.3% in the control group. The adjusted hazard ratio (HR) for TCA use compared with non-use was 1.74 [95% confidence interval (CI) 1.12-2.69, p = 0.01]. Further adjustment for measures of autonomic function reduced the association between TCA use and mortality (HR = 1.27, 95% CI 0.67-2.43, p = 0.47). SSRI use was not associated with mortality (HR = 1.15, 95% CI 0.81-1.64, p = 0.44). CONCLUSIONS: The use of TCA was associated with increased mortality. This association was at least partially mediated by differences in autonomic function. Our findings suggest that TCA should be avoided in patients with coronary heart disease.

Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats.

INTRODUCTION: The neurotrophin brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are a central part of the molecular concepts on neuroplastic changes associated with stress, anxiety and depression. An increasing number of studies uses serum BDNF levels as a potential indicator for central nervous system alterations. METHODS: To analyze the relationship between brain tissue and serum BDNF and NGF levels, we used electroconvulsive shocks (ECS), an animal model of electroconvulsive therapy, and studied the temporal profile of neurotrophin expression in the hippocampus, prefrontal cortex and serum. 88 male Sprague-Dawley rats received single or serial ECS treatments and were killed between 3 hours and 14 days after the last treatment. RESULTS: We found a 2.8-fold rise for BDNF (1.3-fold for NGF) in the prefrontal cortex, and a 2.2-fold rise (1.2-fold for NGF) in the hippocampus after 5 ECS sessions. The temporal expression profile and correlation analyses between tissue and serum BDNF indicate that BDNF crosses the blood-brain barrier. No such correlation was found for NGF. DISCUSSION: The time course of central and peripheral BDNF changes may significantly differ. However, we demonstrate substantial evidence that it can be justified to measure serum BDNF levels with a time delay to monitor brain tissue neurotrophin alterations.

Slow oscillatory transcranial direct current stimulation (so-tDCS) during slow wave sleep has no effects on declarative memory in healthy young subjects.

BACKGROUND: The manipulation of specific brain oscillations by applying transcranial electrical stimulation techniques in order to enhance memory processes during sleep has become an intriguing field of research. A seminal study found a positive effect of slow-oscillatory transcranial direct current stimulation (so-tDCS) on sleep-dependent consolidation of declarative memories. Since then several studies have tried to replicate this result with inconsistent findings. OBJECTIVE/HYPOTHESIS: This study aimed to reexamine effects of so-tDCS on declarative memory observed in young participants based on a previously described stimulation protocol used in elderly subjects. METHODS: 23 healthy participants (mean ±â€¯SD: 23.2 ±â€¯1.9 years; 13 women) completed a word-pair test and a sequential finger tapping test before and after sleep. Participants received anodal so-tDCS bifrontaly at a frequency of 0.75 Hz or sham stimulation during NREM sleep N2, following a double-blind, placebo controlled, counterbalanced, randomized crossover design. Data were analyzed with respect to possible effects of stimulation on memory performances, sleep staging, spindle densities and EEG power in eight frequency bands. RESULTS: Stimulation had no significant effect on sleep dependent memory consolidation or on sleep macro- and microstructure. Independent of stimulation, procedural memory performances increased and declarative memory performances decreased overnight. This decline was less pronounced when participants had more than one learning opportunity. Fast parietal but not slow frontal spindle densities diminished from baseline to stimulation-free intervals under both stimulation conditions. CONCLUSION: The present study could not reproduce the results of the seminal study in young subjects, but it is consistent with results observed in elderly subjects using the same protocol. Irrespective of stimulation, re-encoding opportunities in the word-pair test had an impact on memory strength and retrieval performance.

Age-dependent time course of cerebral brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 in APP23 transgenic mice.

Neurotrophins, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3), have repeatedly been shown to be involved in the pathophysiology of Alzheimer's disease (AD). Recent studies have claimed that these neurotrophic factors are important tools for therapeutic intervention in neurodegenerative diseases. So far, little is known about the age- and disease-modulated time course of cerebral neurotrophins. Therefore, we have studied protein concentrations of BDNF, NGF, and NT-3 in different brain areas and sciatic nerve, a neurotrophin-transporting peripheral nerve, in a well-characterized AD model of amyloid precursor protein-overexpressing rodents (APP23 mice) at the ages of 5.0, 10.5, and 20.0 months. In APP23 mice, there was a significant increase of BDNF and NGF in the frontal and occipital cortices (for BDNF also in the striatum) of old 20.0-month-old mice (with respect to median values up to 8.2-fold), which was highly correlated with amyloid concentrations of these brain areas. Median values of NGF and NT-3 showed up to a 6.0-fold age-dependent increase in the septum that was not detectable in APP23 mice. Hippocampus, olfactory bulb, and cerebellum (except NT-3) did not show substantial age- or genotype-related regulation of neurotrophins. In the sciatic nerve, BDNF and NGF levels are increased in5-month-old APP23 mice and decrease with age to control levels. In conclusion, APP23 mice show a genotype-dependent increase of cortical BDNF and NGF that is highly correlated with amyloid concentrations and may reflect an amyloid-related glia-derived neurotrophin secretion or an altered axonal transport of these neurotrophic factors.

Beta/A4-Amyloid increases nerve growth factor production in rat primary hippocampal astrocyte cultures.

Nerve growth factor (NGF), a member of the neurotrophin family, is an essential mediator of neuronal activity and synaptic plasticity of basal forebrain cholinergic neurons (BFCN). In processes of chronic degeneration of BFCN like in Alzheimer's disease (AD), characterized among others by amyloid containing plaques, NGF has been shown to improve cognitive decline and rescue BFCN but also to reduce survival of hippocampal neurons via p75 neurotrophin receptor (p75). Little is known about the mechanisms of NGF regulation in glial cells under pathological conditions in AD. This study investigates the influence of amyloid administration on the NGF protein secretion in rat primary hippocampal astrocytes. Astrocytes were stimulated with "aged" beta/A4-Amyloid (1-40), and NGF was measured in different fractions, such as supernatant, vesicles, and cytosol fraction. Treatment with amyloid at a final concentration of 10 microM for 72 h led to increased NGF protein levels up to 30-fold increase compared to unstimulated controls. This observation may be an endogenous neuroprotective mechanism possibly contributing to a delay of amyloid-dependent loss of cholinergic neurons or contribute to accelerated neuronal death by activation of p75 within Alzheimer pathology.

Time-of-day variations of indicators of attention: performance, physiologic parameters, and self-assessment of sleepiness.

BACKGROUND: A study was performed to analyze time-of-day variations of different indicators of attention and their interrelations. METHODS: After a sufficiently long all-night sleep 12 healthy non-sleep-deprived subjects ran through a test battery (Stanford Sleepiness Scale, Visual Analogue Scale, Critical Flicker Fusion Test [CFF], Visualization Test, Number Facility Test, Reaction Time, Pupillometry, and modified Multiple Sleep Latency Test) every 2 hours from 7:00 AM until 11:00 PM. Time-of-day variations were tested nonparametrically with Friedman's test for repeated measurements. Principal component factor analysis (of individually standardized values) was used to identify variable complexes with the same pattern of time-of-day variation. RESULTS: Statistically significant time-of-day variations were found for all variables, except for Fusion Frequency in CFF and Reaction Time. In factor analysis the physiologic parameters (pupillometric variables and sleep latencies) load on one factor, whereas the self-assessment scales, the Visualization Test, Number Faculty Test, and CFF load on the second factor. The variables that load primarily on factor 1 show peak levels of alertness immediately after getting up (at 7:00 AM) and again at 9:00 PM. Those variables that load primarily on factor 2 indicate a peak level of alertness around noon (11:00 AM-3:00 PM). CONCLUSIONS: Different aspects of attention follow different time-of-day variations. It is discussed, that these findings can be attributed to underlying circadian and homeostatic factors.

P300 and symptom improvement in schizophrenia.

RATIONALE: A reduced amplitude of the auditory evoked P300 was interpreted as a trait marker of schizophrenia but reports about correlations between schizophrenic psychopathology and P300 amplitude indicate also a state character. OBJECTIVES: To shed light upon these trait and state aspects a longitudinal study was performed to investigate the influence of symptom improvement and atypical neuroleptics on the amplitudes of the P300 and their subcomponents. METHODS: P300 was recorded in 17 schizophrenic patients before and after 4 weeks under either clozapine or olanzapine in a double-blind controlled design. For comparison, 17 age- and sex-matched healthy subjects were investigated. Parietal and frontal P300 subcomponents were investigated separately using dipole source analysis. RESULTS: Schizophrenic patients had smaller parietal (temporo-basal dipole) but not frontal subcomponent amplitudes (temporo-superior dipole) than controls. For the whole sample subcomponent amplitudes did not change over 4 weeks despite clinical improvement but patients with a pronounced improvement of the PANSS positive score showed a slight enhancement of both subcomponents. This was not significant when the P300 amplitude was measured at a single electrode (Pz). No significant difference between clozapine and olanzapine concerning effects on P300 amplitudes were observed. CONCLUSIONS: The results indicate that P300 subcomponents are modulated by changes of positive but not by changes of negative symptoms or different neuroleptics. This result was obvious for P300 subcomponents but not for Pz electrode measurement, which may be due to a higher reliability of the dipole source activity. The results can be integrated into a hypothetical model containing two pathophysiological subgroups of schizophrenia.

Genetic programming approach for the optimal selection of combinations of neuronal networks to classify sleep stages by QUISI.

The usefulness of a new way to optimize the cooperation of trained neural networks for automatic one-channel sleep stage analysis using genetic programming and performance evaluation by including the interrater reliability are the focus of our paper. The one-channel sleep classification could be significantly improved by the optimization. The software tool HENNE, with its genetic programming compartment was developed for this purpose. The tool has proved to be useful for searching for optima in difficult goal surfaces. To contribute to the general discussion about the benefit of the automatic one-channel sleep analysis on the basis of the frontal site, we tried to evaluate our results before the background of the interrater variability. Comparing the kappa statistics of different independent studies with our results, we concluded that there are no dramatic differences as a rule and that QUISI is a useful device as a presleep laboratory and ambulatory diagnostic tool.

Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial.

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (­18 min (P = 0.02)) and WASO (­54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

Persistent deficits of visual recall in Kleine-Levin syndrome.

Kleine-Levin syndrome (KLS) is commonly described as a self-limiting disorder exhibiting episodes of hypersomnia and psychiatric symptoms but without any enduring disabilities. Recently, some authors have reported persistent or even progressive memory deficits associated with the disorder. Nevertheless, literature about cognitive disturbances in KLS is rare. Our report describes a patient with deficits of visual and verbal recall after remission of an episode, as well as selective deficits of visual recall 6 months later. Neuropsychological testing is necessary in all patients with KLS to further characterize the profile and impact of associated cognitive deficits.

The effects of donepezil on postlearning sleep EEG of healthy older adults.

INTRODUCTION: Aging is associated with cholinergic hypofunction and memory decline. Cholinergic activity also plays a crucial role in sleep-dependent memory consolidation. The acetylcholinesterase inhibitor (AChE-I) donepezil has been found to increase sleep-related procedural memory consolidation in healthy older adults in a previous study. METHODS: Data of the former study were reanalyzed with regard to the effects of donepezil on the sleep EEG of healthy older adults. This analysis was conducted with a special focus on spectral parameters of sleep, which have previously been linked to plasticity-related processes during sleep, i.e., sigma and delta activity. Forty-two participants (aged: 60-77 years) received 5 mg of the AChE-I donepezil orally 30 min before bedtime in a placebo-controlled, double-blind design. Power values for EEG delta, theta, alpha1, alpha 2, sigma, beta and gamma frequency bands were calculated for stage 2 NREM sleep, SWS and REM sleep. RESULTS: In line with our hypotheses, the AChE-I donepezil led to an increase in sigma activity during stage 2 NREM sleep and delta activity during slow wave sleep. CONCLUSION: These results suggest that an AChE-I facilitates processes of sleep-dependent memory consolidation in older adults.

The effect of donepezil on sleep in elderly, healthy persons: a double-blind placebo-controlled study.

INTRODUCTION: Previous research in younger individuals has shown that acetylcholinesterase inhibitors tend to enhance REM sleep. METHODS: Forty-two healthy elderly persons participated in a double-blind placebo-controlled polysomnographic study (parallel group design). RESULTS: The present study indicates that in the elderly persons, donepezil, an acetylcholinesterase inhibitor also exerts a marked effect on REM sleep parameters: REM density was increased whereas REM latency was reduced, thus, confirming the findings of our pilot study described earlier. CONCLUSION: Whether the cholinergic stimulation measured by polysomnography is related to treatment efficacy is a very interesting but an open question. Based on the findings that REM sleep is associated with memory consolidation, the question whether REM sleep augmentation enhances memory performance-as suggested by the findings of the pilot study-seems to be an interesting topic for future research.

Differential regulation of nerve growth factor and brain-derived neurotrophic factor in a mouse model of learned helplessness.

Stress-induced helplessness in rodents constitutes a well-defined model to investigate neurobiological mechanisms of depression. Neurotrophins like nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have both been shown to be involved in neurobiological changes of physiological and pathological reactions to stress. In this study we investigated NGF and BDNF protein levels in the frontal cortex and hippocampus in mice treated with an established model of inducible helplessness via electric footshocks compared to untreated controls at various times (0 h up to 14 days after treatment). NGF levels were transiently decreased by one forth in the frontal cortex of shocked mice at 6 h after the stress treatment, whereas BDNF levels remained unchanged in the brain areas investigated throughout the time course. In addition, frontal cortex BDNF levels showed a significantly higher concentration in the right compared to the left hemisphere (up to 3-fold). This effect was detectable independently of treatment, namely in shocked and control mice at any time point measured. In conclusion, a transient decrease of frontal NGF constitutes the most striking correlate of neurobiological changes in this animal model of stress-induced change of behaviour. Interhemispherical differences of BDNF content in the frontal cortex are a new finding that might reflect intracerebral side dominance. Thus, subsequent studies of frontal cortex BDNF expression should carefully consider an interhemispherical variance to avoid misinterpretation.

[Saarland Growth Study: sampling design]. / Saarländische Wachstumsstudie: Sampling Design.

The use of reference data to evaluate the physical development of children and adolescents is part of the daily routine in the paediatric ambulance. The construction of such reference data is based on the collection of extensive reference data. There are different kinds of reference data: cross sectional references, which are based on data collected from a big representative cross-sectional sample of the population, longitudinal references, which are based on follow-up surveys of usually smaller samples of individuals from birth to maturity, and mixed longitudinal references, which are a combination of longitudinal and cross-sectional reference data. The advantages and disadvantages of the different methods of data collection and the resulting reference data are discussed. The Saarland Growth Study was conducted for several reasons: growth processes are subject to secular changes, there are no specific reference data for children and adolescents from this part of the country and the growth charts in use in the paediatric praxis are possibly not appropriate any more. Therefore, the Saarland Growth Study served two purposes a) to create actual regional reference data and b) to create a database for future studies on secular trends in growth processes of children and adolescents from Saarland. The present contribution focusses on general remarks on the sampling design of (cross-sectional) growth surveys and its inferences for the design of the present study.

Serum protein polymorphisms in seven populations from Middle Eastern and Eastern Europe.

Serum specimens from 1385 unrelated males and females from seven Middle East and East European sample surveys (Prague, Olomouc, Krakow, Poznan, Szeged, Moscow, and Jekaterinburg) have been typed for seven polymorphic serum protein polymorphisms (GC, TF, PLG, PI, A2HS, F13B, and ITI). The distributions of phenotype and allele frequencies show a marked heterogeneity, especially with regard to the allel GC*1F of the GC system, the alleles A2HS*1 and A2HS*2 of the A2HS system and the alleles F13B*1 and F13B*3 allele of the F13B system. Analysis of the genetic variability by means of distance and principal component analysis revealed that with regard to the seven polymorphic loci studied the population samples from Prague and Jekaterinburg are characterized by deviating genetic structures. While the different genetic structure of the sample from Prague is mainly due to the distribution of the alleles at the A2HS locus, the sample from Jekaterinburg shows differences in several loci. The genetic dissimilarity corresponds to the large geographic distance from the other populations and can presumably be explained with the comparatively heterogeneous ethnic composition of the population of this city located at the geographic borderline between Europe and Asia.

Secular trends in height, weight and body mass index of 6-year-old children in Bremerhaven.

Secular trends in growth processes of children can be important indicators of changes in public health. Common to studies on secular trends in children is that evaluation is based on comparison of data collected at two (or more) distinct points on a time scale. The quantitative characteristic of the secular trend is estimated by linear interpolation between the two end points of the underlying time interval, which in studies of children are usually at least 10 years apart. The purpose of the present paper is to analyse secular trends in height, weight and body mass index (BMI) of 6-year-old children from Bremerhaven over the period 1968-1987 (the year refers to the birth cohort). The results are based on data drawn from health records of the City Health Centre, where all 6-year-old children are routinely measured in a school entrance examination. Thus the data represent complete birth cohorts of children entering school in Bremerhaven and not selected samples. The data reported here refer only to children of German origin. The sample sizes vary from n = 313 (girls born in 1982) to n = 737 (boys born in 1968), and total sample size is n = 7601. Regression of the arithmetic means of height on year of birth showed that the trend in stature for children born between 1968 and 1987 was 0.67 cm/decade for boys and 0.49 cm/decade in girls. Both trends are statistically significant (p < 0.05). Although there was an increasing tendency for weight as well, which was more marked for the 95th percentile than for the median, neither of the trends in both sexes was statistically significant. While the BMI in both sexes showed no trend at all for the median and the 5th percentile, there was a significant linear increase of the 95th percentile. Furthermore, the results for height show that an evaluation of secular trends under qualitative and quantitative perspective critically depends on the selection of points on the time scale.

[Population biology of northern Germany. 3. Secular changes in the seasonal variation of birth rates in Bremen (from 1826 to 1979)]. / Untersuchungen zur Bevölkerungsbiologie Norddeutschlands. 3. Säkulare Veränderungen der saisonalen Variation der Geburtenhäufigkeiten im Land Bremen (von 1826 bis 1979).

The question, whether the seasonal variation of the birth frequencies are changing with the increase of birthcontrol practice in the population is subject of the present study. The changes of the relevant demographic parameters in this context are discussed first. The study is based on the official monthly records of live- and stillbirths from 1826 to 1979 in Land Bremen (an urban district of northern Germany). For analysis, the material is standardized to equal month length. Trend effects were eliminated using the mean curve. To eliminate stochastic effects, the material is summarized using intervals formed analog to the changes in the birth rate. The means of these intervals illustrate two typical figures; the first is characteristic for the period prior to 1905, the second is characteristic for the years following (excluding the periods from 1915 to 1922 and from 1973 to 1978). The transition of these figures occurred at the change of the century. It is regarded in context with the beginning reduction of birth rate at this time. Whereas for the 19th Century, the seasonal changes, particularly from winter to spring, are regarded as a main cause of physiologic adaptation followed by stimulation of the gonadal gland, "sociologic factors" are taken into account for the seasonality of the birth rates in the 20th Century.

Menarcheal age of Turkish girls in Bremen.

Several studies have shown that there is a Northwest-Southeast gradient in menarcheal age of European girls, with menarche occurring on the average about one year earlier in girls living in the Southern parts of Europe as compared with those from the Northern and Northwestern European countries. Eveleth & Tanner (1976) as well as Danker-Hopfe (1986a) suggested that this gradient is due primarily to genetic differences rather than climatic or nutritional variation. To substantiate this hypothesis menarcheal age of Turkish girls who lived in Bremen for several years has been investigated. The mean age at menarche estimated by probit analysis based on status quo data from n = 494 girls aged from 9.0 to 16.5 years was 12.90 +/- 1.21 years. These results correspond very well to those reported by Neyzi et al. (1975) for girls from Istanbul. On the other hand mean menarcheal age of Turkish girls living in Bremen is distinctly lower than mean age at menarche of urban German girls, living in the same district. In summary the results of the present study support the hypothesis of a predominantly genetic cause for the observed Northwest-Southeast gradient in age at menarche in Europe.